Concordant epidemiological studies have demonstrated that moderate consumption of wine reduces the risk of developing Alzheimer's disease. Several antioxidant polyphenols occur in abundance in wine and are suspected to contribute to the beneficial effect of wine consumption in Alzheimer's disease. Despite skepticism concerning the bioavailability of these polyphenols, recent in vivo data have clearly demonstrated the neuroprotective properties of the naturally occurring polyphenol resveratrol in rodent models for stress and diseases, and consequently, a safety-efficacy study in Alzheimer's disease patients treated with resveratrol is currently conducted at the Mount Sinai School of Medicine. However, the exact molecular mechanisms involved in the beneficial properties of resveratrol and other natural polyphenols on the neurodegenerative process in Alzheimer's disease brain, remain to be clearly defined. Our recent data have revealed that resveratrol (frans-3,4',5-trihydroxystilbene) markedly lowers the levels of amyloid-p peptides in cell culture systems (see appendix 1). The long-term goal of this application is to elucidate the bioavailability of resveratrol and its metabolites in rodents and to characterize their anti-amyloidogenic properties in vitro and in vivo as a necessary prerequisite to the identification of novel complementary and alternative medicines for the prevention of the neurodegenerative mechanisms associated with Alzheimer's disease.